摘要
目的:基于高脂血症大鼠模型和网络药理学技术分析瓜蒌-薤白药对抗高脂血症的作用机制。方法:通过瓜蒌-薤白药对低、中、高剂量(1,2,4 g·kg-1·d-1)预防性给药高脂血症大鼠,检测血脂和炎症因子水平。采用中药系统药理学数据库和分析平台(TCMSP)和文本挖掘筛选瓜蒌-薤白药对活性成分,Swiss Target Prediction,Similarity ensemble approach(SEA),DrugBank数据库筛选与活性成分对应的作用靶点;通过Therapeutic Target Database(TTD),Online Mendelian Inheritance in Man(OMIM),DrugBank和DisGeNET数据库收集疾病靶点。整合交集活性成分的作用靶点和疾病靶点,并通过拓扑学参数筛选,获得瓜蒌-薤白药对抗高脂血症的主要候选靶点。通过ClueGO进行京都基因与基因组百科全书(KEGG)通路富集,the Database for Annotation,Visualization and Integrated Discovery(DAVID)数据库进行基因本体(GO)功能富集分析。通过Cytoscape构建中药-成分-靶点网络模型、靶点-通路网络模型,并分析其串扰靶点和信号通路。结果:动物实验表明,瓜蒌-薤白药对预防性给药可明显降低高脂血症大鼠血清中总胆固醇(TC),甘油三酯(TG),低密度脂蛋白胆固醇(LDL-C)水平,升高高密度脂蛋白胆固醇(HDL-C)水平,抑制白细胞介素-6(IL-6),肿瘤坏死因子-α(TNF-α)表达(P<0.05,P<0.01)。亚油酸乙酯,香叶木素,α-菠菜甾醇等27个活性成分可能是"瓜蒌-薤白"药对主要药效成分,16个串扰靶点和10条信号通路可能是其主要药效靶点和通路;药对主要靶向载脂蛋白A1(APOA1),载脂蛋白A2(APOA2),载脂蛋白C3(APOC3),脂蛋白脂肪酶(LPL),低密度脂蛋白受体(LDLR)等串扰靶点影响胆固醇代谢、胆汁分泌、过氧化物酶体增殖物激活型受体(PPAR)信号通路调节脂质水平;靶向肿瘤坏死因子(TNF),IL-6,IL-1B,丝裂原活化蛋白激酶1(MAPK1),C-C基序趋化因子2(CCL2)等串扰靶点影响TNF信号通路,Toll样受体信号通路,白细胞介素-17(
Objective:Based on the hyperlipidemia rat model and network pharmacology technology,the mechanism of action of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs against hyperlipidemia was analyzed.Method:The levels of blood lipids and inflammatory factors were measured through prophylactic administration of low,medium and high-dose Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs in hyperlipidemia rats.The active ingredients of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs were screened out through Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP)and text mining.The targets of active ingredients screened through the Swiss Target Prediction,Similarity ensemble approach(SEA),DrugBank database.The disease targets were collected through Therapeutic Target Database(TTD),Online Mendelian Inheritance in Man(OMIM),DrugBank,DisGeNET database.The targets of active ingredients and disease target were integrated,and screened through topological parameters to gain the main candidate targets of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs against hyperlipidemia.The Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis and the gene ontology(GO)functional enrichment analysis were conducted through ClueGO and Database for Annotation,Visualization and Integrated Discovery(DAVID),respectively.The traditional Chinese medicinechemical ingredient-target network model,and the target-pathway network model were constructed through Cytoscape,and their crosstalk target and signal pathway were analyzed.Result:Animal experiments showed that the prophylactic administration of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs significantly reduced the levels of total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C)in serum of rats with hyperlipidemia,increased high-density lipoprotein(HDL-C)levels,and inhibited the expressions of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α).According to the
作者
钟华
仇静文
吴鸿飞
徐赫
张鹏
薛程姣
贾鹏程
ZHONG Hua;QIU Jing-wen;WU Hong-fei;XU He;ZHANG Peng;XUE Cheng-jiao;JIA Peng-cheng(School of Pharmacy,Anhui University of Chinese Medicine,Hefei 230000,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2020年第18期154-165,共12页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金项目(81873038)
2018年大学生创新创业训练计划项目(2018173)。
关键词
瓜蒌-薤白药对
高脂血症
血脂
炎症因子
网络药理学
Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs
hyperlipidemia
blood lipid level
inflammatory factor
network pharmacology
